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Using a recently described hamster model of severe yellow fever (YF), we examined the hypothesis that prior infection with heterologous flaviviruses protects against severe or fatal YF. Hamsters were singly or sequentially infected with Japanese encephalitis, St. Louis encephalitis, West Nile, and/or dengue-1 viruses, and then challenged with a virulent strain of yellow fever virus (YFV). In contrast to control (naive) hamsters, many of which appeared clinically ill or died after YFV infection, the flavivirus-immune animals remained asymptomatic. The flavivirus-immune hamsters also had a reduced viremia and lower serum levels of alanine aminotransferase and total bilirubin, compared with naive hamsters, following YFV infection. Histologically, livers of animals in the flavivirus-immune and control groups showed comparable levels of multifocal necrapoptosis. However, steatosis was not observed in the flavivirus-immune animals, whereas naive hamsters developed extensive microvesicular steatosis in the liver following YFV infection. These findings suggest that hepatocytic steatosis is an adverse microscopic feature associated with severe disease in YFV infection. Our experimental results support earlier anecdotal reports that prior exposure of humans to heterologous flaviviruses reduces subsequent risk of fatal YFV infection.
Received December 19, 2002. Accepted for publication March 13, 2003.
Financial support: This study was supported by the National Institutes of Health (grants AI-10984 and AI-50175, NO1-AI-25489) and the Centers for Disease Control and Prevention (grant U50/CCU 620541).
Authors’ addresses: Shu-Yuan Xiao, Department of Pathology and Center for Tropical Diseases, and Department of Internal Medicine, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0588, Telephone: 409-772-8447, Fax: 409-772-4676, E-mail: syxiao{at}utmb.edu. Hilda Guzman, Amelia P. A. Travassos da Rosa, Hong-Bing Zhu, and Robert B. Tesh, Department of Pathology and Center for Tropical Diseases, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0588.
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